DIAZEPAM BIPHASICALLY MODULATES [H-3] TBOB BINDING TO THE CONVULSANT SITE OF THE

2020-04-05 18:34:21

GABA affinity binding diazepam TBOB

责任者: VANRIJN, CM;DIRKSEN, R;WILLEMSVANBREE, E;MAKSAY, G 单位: UNIV NIJMEGEN,NICI,DEPT ANAESTHESIOL,6500 HE NIJMEGEN,NETHERLANDS.;HUNGARIAN ACAD SCI,CENT RES INST CHEM,H-1525 BUDAPEST,HUNGARY. 来源出处: JOURNAL OF RECEPTOR AND SIGNAL TRANSDUCTION RESEARCH, v 15 1995, p 787- 800 摘要: Interactions of GABA, bicuculline methochloride and diazepam with [H-3]TBOB binding to rat brain membranes were evaluated in vitro. GABA displaced [H-3]TBOB binding with and IC50 of 4 mu M and a slope factor near unity. The competitive GABA antagonist bicuculline methochloride shifted the displacement curve of GABA parallelly to the right, indicating that the interaction of GABA with [H-3]TBOB binding is of an allosteric nature. In the presence of GABA, diazepam displaced the binding of [H-3]TBOB according to a two-site model: a high affinity site with an IC50 of about 50 nM and a lower affinity site with an IC50 of about 30 mu M. Bicuculline methochloride abolished the nanomolar displacement by diazepam and increased the micromolar IC50 value. These results indicate that the interaction of the high affinity diazepam site with the [H-3]TBOB binding site is totally GABA dependent and that the low affinity effect of diazepam on [H-3]TBOB binding is at least partially GABA dependent. It is likely that the low affinity potency of diazepam to displace [H-3]TBOB binding has physiological relevance. 关键词: ASTROCYTES; CALCIUM; FLUOXETINE; GLYCOGENOLYSIS; 5-HT RECEPTORS; SEROTONIN SEROTONIN; GAMMA-AMINOBUTYRIC ACID; GATED CHLORIDE CHANNELS; CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN MEMBRANES; BENZODIAZEPINE RECEPTORS; CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN MEMBRANES; BENZODIAZEPINE RECEPTORS; CAGE CONVULSANT; TBPS BINDING; H-3 TBOB; IONOPHORE; AGONISTS CAGE CONVULSANT; TBPS BINDING; H-3 TBOB; IONOPHORE; AGONISTS